Expression Status of IDH1 Mutant and SDHB Genes in Adult and Pediatric Gliomas
Raissa Nobrega, Regia Patrocinio, Phyu P Aung, Jin-Ping Lai, Zengfeng Wang, Markku Miettinen, Kathy Warren, Martha Quezado. National Cancer Institute, National Institutes of Health, Bethesda, MD; BIOPSE Laboratory, Ceara, Brazil; Faculdade de Medicina Christus, Ceara, Brazil
Background: Isocitrate dehydrogenase 1 (IDH1) and Succinate dehydrogenase (SDH) -mutant tumors may express increased HIF stability, which leads to a tumoral pseudohypoxic profile. Increased HIF levels may promote tumor progression by the activation of numerous cellular processes including resistance against apoptosis, vascular remodeling and angiogenesis as well as metastasis. High levels of IDH1 mutations have been frequently detected in adult but not in pediatric gliomas. SDH gene mutation/expression profiles have not been extensively investigated in brain gliomas. To further explore the profile and possible relationship of these metabolism genes in gliomas tumorigenesis, we have investigated the expression of IDH1-mutant and SDH-B in a group of pediatric and adult gliomas by immunohistochemistry.
Design: Samples from 53 patients with gliomas were evaluated. H&E slides were reviewed for confirmation of diagnosis. There were 13 diffuse pontine brain glioma patients (autopsy material), and 40 gliomas in adult patients: 18 low grade (8 astrocytomas, 3 oligodendrogliomas, 2 oligoastrocytomas, 5 ependymomas), 5 high grade oligodendrogliomas, and 17 glioblastomas (GBMs). Immunohistochemistry was done for IDH1mutant (1:250 citric buffer,pH 6.0, Dianova) and SDHB (1:1000, EDTA, pH 8.0, Abcam)
Results: Pediatric brain stem gliomas were negative for mutant IDH1 (0/13) and their SDHB expression was intact (13/13). IDH1 mutant tumors included 11 low grade gliomas (5 astrocytomas, 2 oligodendrogliomas, 3 ependymomas, 1 oligoastrocytoma), 3 high grade oligodendrogliomas and 10 GBMs. No adult glioma exhibits SDHB loss (40/40).
Conclusions: As previously reported, IDH1 mutations are frequently present in low and high grade gliomas and secondary GBMs in adults, but not in pediatric gliomas. No gliomas, pediatric or adult, express SDHB loss/mutation. It appears by our study that the IDH1 but not the SDH metabolism gene is likely to be involved in HIF stabilization in brain tumors. It is unlikely that SDH deficiency contributes to glioma tumorigenesis.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 256, Tuesday Afternoon